The natural cardioprotective particle HDL modulates connexin43 gap junction channels

Abstract

Short-term treatment with HDL or S1P induces phosphorylation of Cx43 by a PKC-dependent pathway. HDL-induced phosphorylation of Cx43 reduced the diffusion of large tracer molecules between cells, whereas impulse conduction was maintained. Moreover, 5 min treatment with HDL confers cardioprotection against ischaemia/reperfusion injury. These results link Cx43 for the first time to the short-term cardioprotective effects of HDL.

Therapeutic Potential of HDL in Cardioprotection and Tissue Repair

“…In agreement with this prior study, rHDL improved cardiac function (Rossoni et al 2004) and reduced infarct size compared to non-treated animals (Gu et al 2007). Recent studies showed that treatment with HDL significantly reduced the infarct size in rodents submitted to IRI compared to non-treated IRI animals (Frias et al 2013;Morel et al 2012). The protective impact of HDL or rHDL did not depend on the timing of injection.…”

“…These studies suggest that the cardioprotective effect involves the activation of the pro-survival proteins ERK1/2 and STAT3, but not p38 MAPK. HDL also induces the phosphorylation of connexin 43 (Morel et al 2012). This phosphorylation leads to a reduction in gap junction permeability, which may limit the spread of mediators implicated in death pathways.…”

“…This phosphorylation leads to a reduction in gap junction permeability, which may limit the spread of mediators implicated in death pathways. Connexin 43 phosphorylation requires the activation of protein kinase C (Morel et al 2012). Although there is not yet direct proof of the implication of connexin 43 in the protective effects of HDL, connexin 43 has been shown to be implicated in ischaemic conditioning (Schulz et al 2007;Schulz and Heusch 2004).…”

Connexin 43 is an emerging therapeutic target in ischemia/reperfusion injury, cardioprotection and neuroprotection

“…Many pharmacological interventions which reduce infarct size after ischemia/reperfusion such as blockade of p38 MAPK (Surinkaew et al, 2013), high density lipoprotein/sphingosine-1 phosphate (Morel et al, 2012), PKC epsilon activating peptide (Lancaster et al, 2011), FGF2/diazoxide (Srisakuldee et al, 2009) or estradiol (Lee et al, 2004) preserved Cx43 phosphorylation during ischemia/reperfusion, although causality between altered Cx43 phosphorylation and reduced infarct size was proven only in one study (Srisakuldee et al, 2009). …”

Lipoproteins: A Source of Cardiac Lipids

“…S1P improves cardiomyocyte survival during hypoxia [ 122 ], protects against doxorubicin toxicity [ 123 ], promotes phosphorylation of connexin 43 [ 124 ] and activates Stat3, a transcription factor with an important role in adaptation of myocardium to stress [ 125 , 126 ].…”